Monthly Archives: November 2001

The use of gene-transfer technology to repair salivary-gland tissue, allowing a pathway for saliva to flow in patients undergoing radiation therapy for head and neck cancer is possible in principle, disclosed Bruce J. Baum, DMD, PhD.

Dr. Baum, who is chief of the Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md., spoke about the breakthrough study to attendees at the American Dental Association’s National Media Conference, held here today.

“We hypothesized that the major impediment to saliva flow from these irradiated, nonsecreting cells was the absence of a pathway for water in their membranes,” he explained. “Our strategy was to transfer a gene for a water channel protein into the radiation-surviving cells that would function as the pathway.”

Each year in the United States, the salivary glands of some 40,000 individuals are exposed to ionizing radiation (IR) during therapy for head and neck cancer. They experience irreversible salivary gland damage. In addition, patients with dry mouth or Sjogren’s syndrome (SS), (an autoimmune disorder characterized by progressive destruction of the lacrimal and salivary glands) also suffer the loss of salivary secretory tissue. Many patients receiving IR or those with SS experience complete gland destruction.

The primary function of salivary glands is to make saliva, the oral fluid that provides the major lubrication and protection for the mouth and upper gastrointestinal tract. In the absence of saliva, patients have difficulty swallowing food, develop mucosal infections like candidiasis, experience rampant dental decay, and suffer considerable pain and discomfort.

“One obvious application for this concept is to augment saliva with gene products for upper-gastrointestinal (GI) tract disorders,” he explained. “Salivary secretions saturate the upper-GI tract lining continuously, and we envision both preventive and healing applications. An alternative strategy is to direct needed therapeutic proteins into the bloodstream for systemic use.”

Using rodent models in studies, we showed that salivary gland repairing and therapeutic applications are possible in principle, he said.

Infection with Helicobacter pylori may increase the risk of developing larynx cancer, researchers from Turkey report.

Dr. Erdinc Aygenc of Ankara Numune Hospital and colleagues screened 26 laryngeal cancer patients and 32 cancer-free subjects for H. pylori infection. About 73% of patients with laryngeal cancer had H. pylori infection, the investigators found, while 41% of those without cancer were infected with the bacterium.

“This study suggests that H. pylori may be an initiator or promoter organism of [larynx cancer], but we cannot say that H. pylori is absolutely the causative agent,” the authors write in the November issue of the journal Otolaryngology-Head and Neck Surgery. For example, they suggest, H. pylori may make laryngeal cells more susceptible to the effects tobacco and alcohol, which are associated with an increase risk of laryngeal cancer. According to the CDC, recent studies have shown an association between long-term H. pylori infection and the development of gastric cancer.

Cancer of the larynx is acommon type of cancer to occur in the head and neck. It is believed to have the same risk factors as oral cancer. Approximately 10,000 Americans will be diagnosed with the disease and roughly 4000 people will die from it in 2001.

Survivors of head and neck cancer generally report more morbidity, including more sexual dysfunction, than survivors of prostate cancer, but age and marital status appear to influence morbidity in both patient groups, according a study reported at the American Society for Therapeutic Radiation and Oncology annual meeting in San Francisco.

Dr. Charles Scott, lead author and statistician for the American College of Radiology, told Reuters Health the findings suggest “cancer survivors are often ill-prepared for the types of impairments that may accompany aggressive treatment.”

For example, Dr. Scott said that head and neck cancer survivors 65 years of age or older are more likely to have speech impairments, but that “younger survivors are more likely to complain about speech impairment. This is probably because younger survivors are more likely to be employed, which makes communication more important.”

Dr. Scott identified head and neck and prostate cancer survivors from the Radiation Therapy Oncology Group database. There were 460 survivors, 276 of whom agreed to participate in a survey that included questions on quality of life, mood, sexual function, alcohol and tobacco use, and mental status.

Twenty-one percent of the patients had head and neck cancers and 79% were prostate cancer patients. The average age of prostate cancer survivors was 75 years, while the average age for the head and neck cancer survivors was 65 years. Twelve percent of the head and neck cancer patients were African American, as were 16% of the prostate cancer patients.

Older head and neck cancer patients reported fewer chronic effects of disease and treatment, and said they had “greater spiritual well-being” than did younger survivors, Dr. Scott said. But regardless of age, head and neck cancer survivors reported “more illness and anger and more sexual dysfunction.” Among prostate cancer survivors, sexual dysfunction was much more common among married survivors, he said.

The findings suggest the need to “be more open when discussing the long-term effects of aggressive treatment,” Dr. Scott concluded. For example, radiation oncologists tend to “tell prostate cancer patients that there is less sexual dysfunction associated with radiation therapy. That’s true, but what if the patient is in that 20% that does experience sexual dysfunction? I don’t think this possibility is well-addressed.”

He also believes the findings suggest clinicians do not adequately assess the needs of older patients in terms of social interactions and sexual relationships. “These very aggressive treatments can have long-term effects and those need to be addressed before treatment begins,” he said.

MGI PHARMA, INC., (Nasdaq:MOGN) today announced that the Radiation Therapy Oncology Group (RTOG) presented final results on data regarding the Company’s Salagen(R) Tablets product at this year’s American Society for Therapeutic Radiology and Oncology (ASTRO) meeting held in San Francisco on November 4-8, 2001. The resulting data were discussed by Dr. Charles W. Scarantino, lead investigator of the RTOG study on Salagen Tablets, in his presentation entitled: “A Phase 3 study on the concurrent use of pilocarpine to reduce hyposalivation and mucositis associated with radiation therapy in head an neck cancer patients – final results of RTOG 97-09.”

Study Data

The RTOG presented data showing that use of Salagen(R) Tablets (pilocarpine hydrochloride), MGI’s approved product to treat the symptoms of radiation-induced dry mouth, gave a statistically significant improvement of salivary flow versus placebo in head and neck cancer patients receiving curative radiation therapy. This Phase 3 trial, with 244 eligible patients, showed the pilocarpine group, who received active drug during radiation therapy and up to six months post therapy, had significantly better salivary flow than did the placebo group at end of radiation therapy, and at three-month and six-month follow-up visits. Based on these findings, RTOG concluded that these results provide new support for the use of Salagen Tablets during radiation treatment.

One of the main side effects of radiation therapy for head and neck cancer patients is dry mouth, a condition that can be permanent, according to Dr. Scarantino, a radiation oncologist with the Rex Healthcare Center, Raleigh, NC, and Southeastern Cancer Control Consortium. “We are quite pleased with the results of the study in that by taking pilocarpine three or four times a day in pill form, salivary flow was better than taking placebo,” said Dr. Scarantino. “These were just the results we were hoping for and we believe we can now build on this study in the future. These clinical results are of real importance to cancer patients.”

Dr. Scarantino said that although the drug had a real impact on dry mouth symptoms, it did not have an effect on mucositis, another side-effect of radiation treatment for head and neck cancer. Mucositis is a painful condition associated with inflammation of the mucous membrane.

About Salagen(R) Tablets

MGI developed and markets Salagen Tablets for the treatment of chronic dry mouth symptoms associated with head and neck cancer patients treated with radiation, and with Sjogren’s syndrome patients. MGI has marketed Salagen Tablets in the United States for the cancer-related indication since 1994 and the Sjogren’s syndrome indication since 1998. Salagen Tablets are the first and only prescription medication approved in the United States for treating dry mouth symptoms associated with both of these patient populations. Chronic dry mouth can be a potentially painful and debilitating condition. Salagen Tablets stimulate the exocrine glands, including the salivary glands, to increase their moisture-producing activity.

When head and neck cancer patients receive radiation treatment, this therapy often damages the salivary glands and their ability to produce moisture. Salagen Tablets can stimulate the glands to generate more moisture.

Salagen Tablets do not work for everyone and are contraindicated when uncontrolled asthma is present and when miosis is undesirable. When used for radiation-induced xerostomia, the most common side effect is sweating. Although less frequent, in some people, headache, flushing, and frequent urination can also occur. When used for Sjogren’s syndrome, the most common side effect is sweating, and in some people, chills, flushing, and frequent urination can occur.

**The Radiation Therapy Oncology Group (RTOG) is a federally funded cancer clinical trials cooperative group, which carries out multi-disciplinary research nationwide. It is a major clinical research component of the American College of Radiology.